This protocol permits the evaluation and treatment of subjects with hereditary and acquired hemolytic diseases, to facilitate understanding of the pathogenesis and natural history of vaso-occlusive painful crisis and pulmonary complications of sickle cell disease and related cardiopulmonary complications of other hereditary, acquired and iatrogenic hemolytic disorders. We will also investigate the polymorphisms that have been linked to pulmonary hypertension to determine whether genetic polymorphisms in candidate genes contribute to the development of pulmonary hypertension or response to treatment. Patients will be evaluated with a medical history and physical examination and routine laboratory studies will be obtained as needed to assess diagnosis, disease activity, and disease complications and to monitor for treatment-related responses and toxicities. Blood can be obtained, with subjects consent, for research studies evaluating gene/protein expression and to evaluate the role of vasodilators, vasoconstrictors, inflammatory and redox stress mediators in this population. Patients identified with pulmonary hypertension will have the option to undergo invasive hemodynamic evaluation and treatment with FDA approved drugs, according to current standards of medical practice, with signed informed consent for all offered procedures. Patients eligible for other research protocols will be offered an opportunity to participate in these studies by signed informed consent. Apart from such protocols, any medical care recommended or provided to the patient will be consistent with routine standards of practice and will be provided in consultation with the patients referring physician. We have successfully enrolled a total of 396 subjects to date. We continue to gather clinical data and experience related to the care of patients with sickle cell disease and other hemolytic disorders. Samples and data collected under this protocol are being used to study the natural history, co-morbid conditions and outcomes, and complications relating to sickle cell disease and other hemolytic disorders in minority/ethnic patients. Samples have been provided to Dr. Lozier (DLM) and Dr. Ballas (Philadelphia, PA) for advanced research blood clotting testing. Samples have been provided to Dr. Casella (Johns Hopkins) for plasma hemopexin and other markers of hemolysis. Frozen blood samples have been sent to Bruce Auerbach (Alphacore Pharma LLC, Ann Arbor MI) for detailed analysis of RBC lipids. Coded samples and data have been sent to Oliver Speer, PhD (University Children's Hospital, Zurich) to measure blood cell micro RNA by microarray or sequencing and for the identification of RNA-protein complexes in blood cells. Corresponding coded DNA samples were also provided for the purpose of sequencing to correlate to micro RNA expression results. Coded samples and echo and clinical data have been sent to Dr. Marc Simon and Dr. Hunter Champion at the University of Pittsburgh for the purpose of analyzing right heart cath data from sickle cell subjects from our Witt monitor, and correlating it to other clinical/echo data. We are analyzing the walk-PHaSST data (protocol 07-H-177) for echo predictors of exercise limitations and will corroborate with data from cardiac catheterizations. Echo and cardiac catheterization correlations from our NIH cohort (including this protocol) will help us validate echo measures of diastolic dysfunction for use in the walk-PHaSST dataset.